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| 1 | Wnt signaling and Loxl2 promote aggressive osteosarcoma显示文摘Osteosarcoma(OS)is the most frequent primary malignant bone tumor in urgent need of better therapies.Using genetically modified mouse models(GEMMs),we demonstrate that Wnt signaling promotes c-Fos-induced OS formation via the actions of the collagen-modifying enzyme Loxl2.c-Fos/AP-1 directly regulates the expression of the Wnt ligands Wnt7b and Wnt9a in OS cells through promoter binding,and Wnt7b and Wnt9a in turn promote Loxl2 expression in murine and human OS cells through the transcription factors Zeb1 and Zeb2.Concordantly,inhibition of Wnt ligand secretion by inactivating the Wnt-less(Wls)gene in osteoblasts in c-Fos GEMMs either early or in a therapeutic setting reduces Loxl2 expression and progression of OS.Wls-deficient osteosarcomas proliferate less,are less mineralized and are enriched in fibroblastic cells surrounded by collagen fibers.Importantly,Loxl2 inhibition using either the pan-Lox inhibitor BAPN or a specific inducible shRNA reduces OS cell proliferation in vitro and decreases tumor growth and lung colonization in murine and human orthotopic OS transplantation models.Finally,OS development is delayed in c-Fos GEMMs treated with BAPN or with specific Loxl2 blocking antibodies.Congruently,a strong correlation between c-FOS,LOXL2 and WNT7B/WNT9A expression is observed in human OS samples,and c-FOS/LOXL2 co-expression correlates with OS aggressiveness and decreased patient survival.Therefore,therapeutic targeting of Wnt and/or Loxl2 should be considered to potentiate the inadequate current treatments for pediatric,recurrent,and metastatic OS. | Kazuhiko Matsuoka Latifa Bakiri Lena I.Wolff Markus Linder Amanda Mikels-Vigdal Ana Patiño-García Fernando Lecanda Christine Hartmann Maria Sibilia Erwin F.Wagner | 2020 | Cell Research2020，30，10： | 5 |
| 2 | Epithelial to mesenchymal transition and cancer stem cell phenotypes leading to liver metastasis are abrogated by the novel TGFβ1-targeting peptides P17 and P144显示文摘 | Idoia G. Zubeldia Anne-Marie Bleau Miriam Redrado Diego Serrano Alice Agliano Carmen Gil-Puig Fernando Vidal-Vanaclocha Jon Lecanda Alfonso Calvo | 2012 | Experimental Cell Research2012，，： | 2 |
| 3 | Connexin43deficiency causes delayed ossification, craniofacial abnormalities,and osteoblast dysfunction显示文摘 | LECANDA F WARLOW P M SHEIKH S | 2000 | J Cell Biol2000，151，4： | 1 |
| 4 | Differential regulation of cadherins by dexamethasone in human osteoblastic cells 显示文摘 | Lecanda F Cheng SL Shin CS | 2000 | J Cell Biochem2000，77，3： | 1 |
| 5 | Dynamical Encoding by Networks of Competing Neuron Group:Winnerless Competition显示文摘 | Volkovskii A Lecanda P | 2001 | Phys Rev lett2001，68，： | 1 |
| 6 | Differential regulation ofcadherins by dexamethasone in human osteoblastic cells显示文摘 | Lecanda F Cheng SL Shin CS | 2000 | J Cell Biochem2000，77，3： | 1 |
| 7 | VEGF elicitsepithelial-mesenchymal transition(EMT)in prostate intraepi-thelial neoplasia(PIN)-like cells via an autocrine loop显示文摘 | Gonzalez-Moreno O Lecanda J Green J E | 2010 | Exp Cell Res2010，316，4： | 1 |
| 8 | Connexin43 deficiency causes delayed ossification,craniofacial abnormalities,and osteoblast dysfunction显示文摘 | Lecanda F Warlow PM Sheikh S | 2000 | Journal of Cell Biology2000，151，： | 1 |
| 9 | Dynamical encoding by networks of competing neuron groups: winnerless competition 显示文摘 | Rabinovich M Volkovskii A Lecanda P | 2001 | Phys Rev Lett2001，87，： | 1 |
| 10 | In vivo gene transfer of CD40 ligand into colon cancer cells induces local production of cytokines and chemokines, tumor eradication and protecftive antitumor immunity显示文摘 | Sun Y Peng K Lecanda J | 2000 | Gene Ther2000，7，： | 1 |
| 11 | Transforming growth factorbeta,estrogen, and progesterone converge on the regulation ofp27Kip1 in the normal and malignant endometrium显示文摘 | Lecanda J Parekh TV Gama P | 2007 | CancerRes2007，67，3： | 1 |
| 12 | Imparied intramembranous bone formation in connexin 43 nullmice显示文摘 | Lecanda F Warlow P Halstead LR | 1998 | Bone1998，，： | 1 |
| 13 | Regulation of bone matrix protein expression and induction of differentiation of human osterblast and human bone marrow stromal cells by bone morphogenetic protein-2 显示文摘 | Lecanda F Avioli LV Cheng SL | 1997 | J Cell Biochem1997，67，3： | 1 |
| 14 | Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2显示文摘 | Lecanda F Avioli LV Cheng SL | 1997 | J Cell Biochem1997，67，3： | 1 |
| 15 | VEGF elicits epi- thelial-mesenchymal transition (EMT) in prostate intraepithelial neo- plasia (PIN)-like cells via an autocrine loop 显示文摘 | Gonzalez-Moreno O Lecanda J Green JE | 2009 | Exp Cell Res2009，316，4： | 1 |
| 16 | VEGF e- licits epithelial-mesenchymal transition (EMT) in prostate intraepitheliai neoplasia (PIN)-like cells via an autocrine loop 显示文摘 | Gonzalez-Moreno O Lecanda J Green JE | 2010 | Exp Cell Res2010，316，： | 1 |
| 17 | Relative abundance of differ-ent cadherins defines differentiation of mesenchymal precursors intoosteogenic,myogenic,or adipogenic pathways 显示文摘 | Shin C S Lecanda F Sheikh S | 2000 | J Cell Biochem2000，78，4： | 1 |
| 18 | Connexin43 deficiency causes delayed ossification, craniofacial abnormalities, and osteohlast dysfunction显示文摘 | Lecanda F Warlow PM Sheikh S | 2000 | J Cell Biol2000，151，4： | 1 |
| 19 | Dynamical encoding by networks of compe-tingneuron group:Winnerless competition显示文摘 | RABINOVICH M VOLKOVSKII A LECANDA P | 2001 | Phys Rev Lett2001，87，： | 1 |
| 20 | Shared apical sorting of anion exchanger isoforms AE2a, AE2b 1 , and AE2b 2 in primary hepatocytes显示文摘 | Victoria Aranda I?igo Mart??nez Saida Melero Jon Lecanda Jesús M. Banales Jesús Prieto Juan F. Medina | 2004 | Biochemical and Biophysical Research Communications2004，，3： | 1 |
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